Myocardial infarction is one of the leading causes of death and disability worldwide, and there is an urgent need for novel cardioprotective or regenerative strategies. An essential component of drug development is determining how a novel therapeutic is to be administered. Physiologically relevant large animal models are of critical importance in assessing the feasibility and efficacy of various therapeutic delivery strategies. Due to their similarities to humans in cardiovascular physiology, coronary vascular anatomy, and heart weight to body weight ratio, swine is one of the preferred species in the preclinical evaluation of new therapies for myocardial infarction. The present protocol describes three methods of administering cardioactive therapeutic agents in a porcine model. After percutaneously induced myocardial infarction, female landrace swine received treatment with novel agents through either: (1) thoracotomy and transepicardial injection, (2) catheter-based transendocardial injection, or (3) intravenous infusion via jugular vein osmotic minipump. The procedures employed for each technique are reproducible, resulting in reliable cardioactive drug delivery. These models can be easily adapted to suit individual study designs, and each of these delivery techniques can be used to investigate a variety of possible interventions. Therefore, these methods are a useful tool for translational scientists pursuing novel biological approaches in cardiac repair following myocardial infarction.
Myocardial infarction is one of the leading causes of death and disability worldwide, and there is an urgent need for novel cardioprotective or regenerative strategies. An essential component of drug development is determining how a novel therapeutic is to be administered. Physiologically relevant large animal models are of critical importance in assessing the feasibility and efficacy of various therapeutic delivery strategies. Due to their similarities to humans in cardiovascular physiology, coronary vascular anatomy, and heart weight to body weight ratio, swine is one of the preferred species in the preclinical evaluation of new therapies for myocardial infarction. The present protocol describes three methods of administering cardioactive therapeutic agents in a porcine model. After percutaneously induced myocardial infarction, female landrace swine received treatment with novel agents through either: (1) thoracotomy and transepicardial injection, (2) catheter-based transendocardial injection, or (3) intravenous infusion via jugular vein osmotic minipump. The procedures employed for each technique are reproducible, resulting in reliable cardioactive drug delivery. These models can be easily adapted to suit individual study designs, and each of these delivery techniques can be used to investigate a variety of possible interventions. Therefore, these methods are a useful tool for translational scientists pursuing novel biological approaches in cardiac repair following myocardial infarction.
Introduction and importance: Basosquamous carcinoma (BSC) is a rare cutaneous cancer defined as a basal-cell carcinoma that has differentiated into a squamous-cell carcinoma. It is aggressive and infiltrative, and known for its multiple recurrences and risk for metastasis.Case presentation: This article describes the case of a 78-year-old man who presented with a several-year history of an infiltrative BSC of his chest-wall invading into his sternum.Clinical discussion: He was subsequently treated surgically with a chest-wall wide-local excision and sub-total sternectomy, reconstructed with titanium plates and a musculocutaneous anterolateral thigh free-flap.Conclusion: This case highlights a surgical approach to advanced chest-wall BSC.
Background Exciting pre-clinical data have confirmed that human pluripotent stem cell derived cardiomyocytes (PSC-CMs) can remuscularise the injured or diseased heart, with several clinical trials now in planning or recruitment stages worldwide. However, ventricular arrhythmias are a predictable complication following engraftment of intramyocardially injected PSC-CMs. Therefore, there is an urgent unmet need to gain mechanistic insights and treatment strategies to control or prevent these engraftment arrhythmias (EAs). Methods We used a porcine model of myocardial infarction and PSC-CM transplantation to investigate efficacy of pharmacologic and catheter based anti-arrhythmic strategies in mitigating EAs. Furthermore, cell doses were robustly phenotyped using single cell ribonucleic acid sequencing and high parameter flow cytometry to identify cellular characteristics predictive of arrhythmogenesis. Results Combination therapy with amiodarone and ivabradine significantly reduced EA rate and burden following PSC-CM transplantation. Catheter ablation was also a feasible and effective treatment strategy which could be considered in the case of pharmacologically refractory arrhythmias. In addition, we show that EAs are mechanistically linked to cellular heterogeneity in the input PSC-CM and resultant graft. Specifically, we identify atrial and pacemaker-like cardiomyocytes as culprit arrhythmogenic subpopulations. We further describe two unique surface marker signatures, SIRPA + /CD90 - /CD200 + and SIRPA + /CD90 - /CD200 - , which identify arrhythmogenic and non-arrhythmogenic cardiomyocytes respectively. Conclusion Our data deepens mechanistic understanding of EAs and suggests that modifications to current PSC-CM production and/or selection protocols could ameliorate this problem. We further show that current clinical pharmacologic and interventional anti-arrhythmic strategies can control and potentially abolish these arrhythmias, an important safety consideration given several impending clinical trials.
Lamin A/C (LMNA) cardiomyopathy forms an important and increasingly recognised group within the broad spectrum of non-ischaemic cardiomyopathies. LMNA cardiomyopathy typically presents with atrioventricular block followed by recurrent ventricular arrhythmias with a high tendency to progression to end stage heart failure. We present a case of recurrent ventricular tachycardia in a patient with dilated cardiomyopathy caused by a novel mutation of LMNA gene. Through electroanatomic mapping, catheter ablation and tissue pathology we provide detailed insights into this highly pathogenic inherited cardiomyopathy.
BACKGROUND:Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide circulatory support in high-risk patients undergoing drug refractory ventricular tachycardia (VT) ablation procedures. We report experience using VA-ECMO in a pre-emptive approach for high-risk patients with VT storm and previously ineffective ablation procedures. METHODS AND RESULTS:Four (4) patients with drug refractory ventricular tachycardia (mean age 61±3 years; left ventricular ejection fraction 21±5%) presenting for VT ablation had pre-emptive VA-ECMO. All patients during current admission had VT storm. Pre-ablation, 22 total monomorphic VTs (cycle length 402±69 ms) were induced or spontaneously observed (median of 4, IQR25-75% 1-6). At the end of the procedure, 86% of all inducible VTs were rendered non-inducible. Median hospitalisation following VA-ECMO supported ablation was 5 days (IQR25-75% 3-12). During follow-up (median 138 days [IQR25-75% 57-277]), VT recurred in one patient as an isolated episode reverted by anti-tachycardia pacing. There was a 99% reduction in VT burden post ablation. One (1) patient died of cardiogenic shock within 24 hours whilst still on VA-ECMO, all other patients were successfully weaned off support and discharged. Two (2) patients underwent cardiac transplantation at 199 and 512 days post ablation following implantation of ventricular assist devices for worsening heart failure. CONCLUSIONS:The pre-emptive use of VA-ECMO for high-risk patients undergoing catheter ablation for VT storm was found to be effective in maintaining haemodynamic status, and allowing successful mapping and catheter ablation for VT.
Purpose: Tension chylothorax is a sequelae of undiagnosed post-pneumonectomy chylothorax (PPC), which is a rare but likely under-reported complication following pneumonectomy. Unless promptly recognised and managed, tension chylothoraces lead to haemodynamic compromise and high morbidity and mortality. There is currently no consensus for treatment, with reported management strategies predominantly advocating for early surgical exploration and thoracic duct ligation. Few cases of successful conservative management have been reported. This study reported experience with tension chylothoraces.
Background: Mid-aortic syndrome is a rare condition where the distal thoracic and or abdominal aorta is severely narrowed. The renal arteries and visceral branches of the aorta are often involved [ 1 Tummulo A. Marks S.D. Stadermann M. et al. Mid-aortic syndrome: long-term outcome of 36 children. Pediatr Nephrol. 2009; 24: 2225-2232https://doi.org/10.1007/s00467-009-1242-6 Crossref Scopus (68) Google Scholar , 2 Disease Beyond the Arch: A Systematic Review of Middle Aortic Syndrome in Childhood. Am J Hypertens 2015; 28(7):833-46. https://doi.org/10.1093/ajh/hpu296 Google Scholar ]. The surgical management of this condition has not been described in Australasian literature.
A floating giant aortic thrombus is a rare finding in the absence of any coagulation disorder. Patients usually remain asymptomatic until the development of embolic complications. Our report highlights cocaine abuse as a potential cause of aortic thrombus and bowel perforation. Clinicians should have a high index of suspicion when treating patients with a history of illicit cocaine use with signs and symptoms of arterial ischemia. The risks of cardiovascular and abdominal complications related to cocaine use should not be underestimated. Prompt diagnosis is required to circumvent potentially life-threatening complications.
Purpose: Transcatheter aortic valve implantation (TAVI) for aortic stenosis has been increasing, as demonstrated in the UK TAVI Registry Report. As TAVI patients are normally high-risk elderly patients, we undertook a propensity-matched study to compare outcomes of surgical aortic valve replacement (sAVR) with TAVI in order to exclude the confounding differences between patient groups that normally have surgery versus those with transcatheter procedures. Methodology: A retrospective review of our institution's aortic surgery database with propensity score matching was undertaken to compare outcomes of sAVR versus TAVI. Data for this database is prospectively entered. Results: There were 2,102 sAVR and 260 TAVI performed between 2008-2016 with significant differences in most of their preoperative characteristics such as EuroSCORE (6.0 vs 17.3) and age (72 vs 84 years). After propensity score matching, there were 179 patients in each group with no significant differences in their preoperative characteristics. There were no significant differences between groups with respect to in-hospital mortality (4.5% in each group), stroke (1.7% sAVR vs 2.2% TAVI), postoperative myocardial infarction (0.1% vs 0%) or pacemaker implantation (3.4% vs 3.9%). Hospital (11 vs 7 days) and critical care (3 vs 2 days) length of stay were higher in the sAVR group. There was a significant difference between groups in actuarial survival rates at 1-year (89.6% (sAVR) and 85.0% (TAVI)) and 5 years (62.7% and 43.2%). Conclusion: In our institution, in-hospital short-term outcomes are comparable between sAVR and TAVI. However, long-term survival is more favourable in those having a surgical approach to valve replacement than transcatheter routes.
Purpose: The optimal strategy to minimise neurological morbidity and mortality following acute type A aortic dissection repair is unclear and remains controversial. There are a number of strategies employed, which include deep hypothermic circulatory arrest (DHCA), retrograde cerebral perfusion (RCP) and antegrade cerebral perfusion (ACP). This study was designed to examine the outcomes of a variety of cerebral protection strategies used in our institution for acute type A dissection repair. Methodology: A retrospective review of our institution's aortic surgery database was undertaken to compare outcomes of various cerebral protection strategies in acute type A dissection repairs. These included DHCA only, hypothermic circulatory arrest with ACP and hypothermic circulatory arrest with RCP. Data for this database was prospectively entered. Results: Preoperative characteristics between groups were similar. A variety of repair techniques were employed in the dissection repairs, including root replacement, ascending aorta, hemiarch and total arch replacement. Preliminary data analysis demonstrated that there were no significant differences between groups with regard to in-hospital mortality, stroke or reoperation for bleeding. Preliminary 3-year survival plots demonstrated no significant differences between groups. Conclusion: Preliminary analysis of the outcomes in type A dissection repairs in our institution have shown that the different cerebral protection strategies do not have a significant impact on outcomes. However, these results need to be considered in the context of the limitations of a retrospective analysis. Further analyses of this data will be undertaken.
Purpose: Despite its reported benefits over open surgery, video assisted thoracoscopic (VATS) lung resections still make up < 50% of cases in many countries. In the United Kingdom, the SCTS thoracic registry data reported VATS resection made up 40% of all lobectomies for lung cancer in 2014-15. This study examines the experience and outcomes of VATS versus open lobectomy in a single high volume centre. Methodology: A retrospective review of our institution's thoracic surgery database was undertaken to examine the results of lobectomies performed from December 2010 to July 2016. Complex lung resections were excluded from this study. Morbidity, lymph node and tumour staging, and mortality were investigated between groups. Results: 469 VATS and 1237 open lobectomies were examined. The average age was 69 yrs (31-89) and 68 yrs (14-90) respectively. 10% of VATS patients were octogenarians vs 8.6% in the open group. Average preoperative FEV1 values were 87% and 86% predicted. Median length of stay was 4 days (VATS) vs 6 days (open); critical care re-admission 2.63% vs 5.58%; and in-hospital mortality 0.21% vs 2.26%. Atrial fibrillation occurred in 5.97% (VATS) vs 5.66% (open), and prolonged air leak in 4.48% vs 6.47%. R0 resection was achieved in 100% (VATS) vs 99.35% (open). Numbers and site of lymph nodes sampled at time of surgery were also assessed. Conclusion: VATS lobectomy is safe in our institution and is increasing as a proportion of total lung resections. Patient demographics were comparable between groups. Length of stay and in-hospital mortality were both significantly decreased in the VATS group. Rates of AF were similar with a trend towards decreased air leak in the VATS group.
Purpose: Despite literature demonstrating superiority of arterial grafts over saphenous vein grafts (SVG), there is still low usage of arterial grafting in coronary artery bypass surgery. Less than 10% of patients on the Society of Thoracic Surgeons cardiac database received a second arterial graft and its use remains a matter of debate. We examined the experience of arterial revascularisation versus left internal mammary artery (LIMA) and SVG at our institution, and their outcomes. Methodology: A retrospective review of our institution's cardiac surgery database (1998-2016) with propensity score matching was undertaken to compare outcomes of 2 or more arterial grafts versus LIMA+SVG. Data for this database is prospectively entered. Results: There were 3,888 multiple arterial grafting (MAG) and 10,111 LIMA+SVG patients. After propensity matching, 3,206 patients were identified in each group. There were no significant differences in preoperative characteristics between groups. There were no differences between groups in post-operative acute renal failure, stroke, deep sternal wound infection or in-hospital mortality. Postoperative myocardial infarction was higher in the MAG group and atrial arrhythmias higher in the LIMA+SVG group. Matched 15 year survival curves demonstrated no significant differences between groups. Conclusion: Within the limitations of this study, we have found that in our centre, the choice of conduit does not affect survival for up to 15 years. There were also no differences in most in-hospital complications between groups. In spite of international literature reporting that arterial revascularisation is associated with better outcomes, we were unable to demonstrate this in our patient cohort.
Introduction. The systemic effects of brain death (BD) are major mediators of donor organ dysfunction, contributing to donor haemodynamic instability and morbidity/mortality in the transplant recipient.
The success of organ transplantation is critically dependent on the quality of the donor organ. Donor organ quality, in turn, is determined by a variety of factors including donor age and preexisting disease, the mechanism of brain death, donor management prior to organ procurement, the duration of hypothermic storage, and the circumstances of reperfusion. It has been recognized for some time that both the short- and long-term outcomes after cadaveric organ transplantation are significantly inferior to those obtained when the transplanted organ is obtained from a living donor, regardless of whether the donor is related or unrelated to the recipient. Brain death results in a series of hemodynamic, neurohormonal, and pro-inflammatory perturbations, all of which are thought to contribute to donor organ dysfunction. The process of transplantation exposes the donor organ to an obligatory period of ischemia and reperfusion. Traditionally, hypothermic storage of the donor organ has been used to protect it from ischemic injury, but donor organs differ markedly in their capacity to withstand hypothermic ischemia. Data from the Registry of the International Society for Heart and Lung Transplantation indicate that the risk of primary graft failure and death rises dramatically for both the heart and lung as ischemic time increases. Based on these data, maximum recommended ischemic times for the donor heart and lung are 6 and 8 h, respectively. In this chapter, strategies aimed at minimizing the adverse consequences of brain death and ischemia/reperfusion injury to the donor heart and lung are discussed. These strategies are likely to become increasingly important as the reliance on marginal donors increases to meet the growing demand for organ transplantation.